The invention concerns a process for the manufacture of solid drug formulations or dosage units, and in particular, a process in which special pharmaceutical adjuvants and additives are used to produce preparations with specific dissolution, disintegration and liberation properties.
In the manufacture of solid drug formulations, it is generally a paramount objective to provide the active agents in such a form that they display certain rates, durations and strengths of activity. Preparation and administration of these active agents is no longer carried out without a consideration of their behavior in the organism. There are known numerous galenic methods which influence the availability of the active agents, as well as the parameters of activity dependent thereon. The effect achieved through the use of such agents may variously be an acceleration or a delay of availability; discontinous as well as uniform effects may be achieved. The types of processes commonly involved may be subdivided for convenience into those which influence the dissolution rate and those which change the diffusion or permeation rate. A faster liberation of the active agent, for example, may be effected by surface enlargement (e.g. crushing), amorphization or addition of solubilizers; a delayed liberation is made possible by embedding the active agent into or coating it with substances which are only soluble with difficulty.
The present invention is concerned with the development of a novel procedure for delaying the dissolution and thus obtaining a retarding effect. This problem has in principle been dealt with by numerous procedures: methods in which the active agent particles or the whole dosage unit (e.g., tablet, capsule) is located with a film; those in which the active substance is incorporated into an erosive hard fat bed; those in which the active agent is polymerized into a synthetic material; those in which the active agent is pressed or tabletted with a plastic material; and those in which the agent is bound to an insoluble carrier, such as an ion-exchange resin. With each of these procedures, there is either only a limited range of variability or else an additional operational stage in the preparation is required. Moreover, the use of certain matrix-forming agents determines to a large extent the properties of the product units. Other methods, in particular coating processes, require specialized technology.